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Cell Rep. 2017 Jan 10;18(2):557-570. doi: 10.1016/j.celrep.2016.12.011.

Major Shifts in Glial Regional Identity Are a Transcriptional Hallmark of Human Brain Aging.

Author information

  • 1Institute of Neurology, University College London, London WC1N 3BG, UK; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
  • 2MRC Edinburgh Brain Bank, Academic Neuropathology, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK.
  • 3The Computational, Cognitive and Clinical NeuroImaging Laboratory, Division of Brain Sciences, Imperial College, London SW7 2AZ, UK.
  • 4Institute of Neurology, University College London, London WC1N 3BG, UK; Reta Lila Weston Institute of Neurological Studies, UCL ION, 1 Wakefield Street, London WC1N 1PJ, UK.
  • 5Institute of Neurology, University College London, London WC1N 3BG, UK; Departments of Genetics, King Faisal Specialist Hospital and Research Centre. Riyadh 12713, Saudi Arabia.
  • 6Laboratory of Neurogenetics, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
  • 7Institute of Neurology, University College London, London WC1N 3BG, UK; Department of Medical and Molecular Genetics, King's College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK.
  • 8Institute of Neurology, University College London, London WC1N 3BG, UK; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK; Reta Lila Weston Institute of Neurological Studies, UCL ION, 1 Wakefield Street, London WC1N 1PJ, UK; Euan MacDonald Centre for MND, University of Edinburgh, Edinburgh EH8 9YL, UK; Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 1TN, UK. Electronic address: rickie.patani@ucl.ac.uk.
  • 9Institute of Neurology, University College London, London WC1N 3BG, UK; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK. Electronic address: j.ule@ucl.ac.uk.

Abstract

Gene expression studies suggest that aging of the human brain is determined by a complex interplay of molecular events, although both its region- and cell-type-specific consequences remain poorly understood. Here, we extensively characterized aging-altered gene expression changes across ten human brain regions from 480 individuals ranging in age from 16 to 106 years. We show that astrocyte- and oligodendrocyte-specific genes, but not neuron-specific genes, shift their regional expression patterns upon aging, particularly in the hippocampus and substantia nigra, while the expression of microglia- and endothelial-specific genes increase in all brain regions. In line with these changes, high-resolution immunohistochemistry demonstrated decreased numbers of oligodendrocytes and of neuronal subpopulations in the aging brain cortex. Finally, glial-specific genes predict age with greater precision than neuron-specific genes, thus highlighting the need for greater mechanistic understanding of neuron-glia interactions in aging and late-life diseases.

KEYWORDS:

RNA-seq; aging; brain; exon microarrays; gene expression; immunohistochemistry; machine learning; microglia; neurons; olgiodendrocytes

PMID:
28076797
PMCID:
PMC5263238
DOI:
10.1016/j.celrep.2016.12.011
[PubMed - in process]
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